tbuckley/cabot-search huggingface dataset:
Abstract 9555: Human Valve Atlas in Health and Disease
Authors: Ziyi Liu, Yu Liu, Zhiyun Yu, Anna O'Donnell, Minzhe Guo, Ya-Wen Chen, Ian Glass, Katherine Yutzey, Joseph Wu, Yifei Miao, Mingxia Gu
Journal: Circulation (2022)

Background: Semilunar and atrioventricular valves have distinct structures and are often affected differently in congenital valve diseases (CVD). Here we aim to define and compare the cellular composition and transcriptomic signatures of four different human fetal valves, which provide a reference map to engineer valves in vitro , and to study valve-specific impairment in CVD. Methods: Aortic, pulmonary, mitral, and tricuspid valves were barcoded respectively from a healthy human fetal heart at gestational day 105. Single-cell (sc)RNA-seq was performed. Spatial localization of new subpopulations was determined by immunostaining and in situ hybridization. Cell-cell interaction was revealed by cell-chat. Results: scRNA-seq analysis revealed major cell types including endothelial (VECs), interstitial (VICs), and immune cells. In addition to reported collagen &amp; glycosaminoglycan (GAG) VIC in mice, VIC sub-clustering identified two human-specific APOE+ and CLDN11+ subpopulations. APOE+ VICs specifically located underneath VECs facing unidirectional flow, indicating cell-cell interaction of APOE+ VICs &amp; VECs. VEC sub-clustering identified lymphatic VECs under turbulent flow, while CD55+ &amp; PTGDS+ VECs under unidirectional flow. Cell-chat uncovered NOTCH3-JAG1 pairs in facilitating the co-development of spatially adjacent APOE+ VICs &amp; PTGDS+ VECs. To further uncover valve-specific signatures, we compared gene expression profiles of four valves. In lymphatic VECs, genes regulating BMP pathway were enriched in semilunar valves. In GAG VICs, MAPK pathway was specifically enriched in pulmonary valve, indicating development of different valves may need activation of different pathways. Interestingly, when comparing valve with pulmonary atresia versus healthy pulmonary valve using scRNA-seq, both MAPK related genes and GAG VICs were significantly reduced, suggesting impaired MAPK may contribute to pulmonary-specific loss of GAG VICs leading to its abnormal development. Conclusion: Our high-resolution atlas of human fetal valves revealed subtypes of VIC &amp; VEC with unique spatial locations. Comparison of four valves identified pulmonary valve-specific MAPK pathway that may explain loss of GAG VICs in patients with pulmonary atresia.
Abstract 9345: Midline1 is a Critical Regulator of Viral Myocarditis
Authors: Junji Xing, Mingli Fang, Wenting Lu, Junying Wang, Zhiqiang Zhang
Journal: Circulation (2022)

Introduction: Infections by viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could cause viral myocarditis. Innate immunity to viral nucleic acids mediates antiviral immunity as well as inflammatory organ injury. However, the innate immune mechanisms that control the pathogenesis of viral myocarditis are unclear. Methods: To understand the role of the E3 ligase Midline1 in controlling viral myocarditis, wild-type and Midline1 knockout mice were infected with coxsackievirus B3 (CVB3) or encephalomyocarditis (EMCV) for inducing viral myocarditis. Mice survivals and heart functions were monitored by transthoracic echocardiography, and hearts were harvested for histology analysis. Real-time PCR, western blotting, co-immunoprecipitation, enzyme-linked immunoassay, luciferase assay, flow cytometry, over-expression and knockdown techniques were used to understand the molecular mechanisms of Midline1 in regulating type I interferon production after virus infection in this study. Results: We find that Midline1 is induced by RNA viruses with heart tropisms CVB3 and EMCV. Knockdown or deletion of Midline1 in human or mouse macrophages enhances production of type I interferon (IFN) in response to double strand (ds) RNA, RNA viruses CVB3 or EMCV. Importantly, deletion of Midline1 protects mice from viral myocarditis induced by CVB3 or EMCV due to enhanced type I IFN production in vivo. Mechanistically, we show that Midline1 recruits protein phosphatase 1A (PPM1A) to dephosphorylate TANK binding kinase 1 (TBK1), which inactivates TBK1 to block TBK1 from interacting with its upstream adaptor mitochondrial antiviral signaling (MAVS), thereby dampening antiviral signaling during viral infections. Moreover, Midline1 stabilizes PPM1A by inducing K63-linked ubiquitination of PPM1A. Conclusions: Our results indicate that Midline1 serves as a negative regulator of viral myocarditis by downregulating innate immune activation induced by RNA viruses CVB3 and EMCV. Our data reveal that Midline1 is a critical regulator of innate immunity in viral myocarditis, thereby identifying a potential therapeutic target for treating viral induced cardiovascular diseases.
Abstract 9703: Cardiac β <sub>3</sub> -Adrenergic Receptor Deficiency Mice Protected from Cardiac Aging: Insights into the Cellular and Molecular Mechanism of Myocardial Aging
Authors: Che Ping Cheng, Zhe Chen, Peng Zhou, Yixi Liu, David M Herrington, David X Zhao, Dalane W Kitzman, Heng-Jie Cheng
Journal: Circulation (2022)

Background: We have shown previously that aging-caused declines in cardiac function and β-adrenergic reserve were prevented in β 3 -adrenergic receptor (AR) knockout (β 3 KO) aged mice. The cellular and molecular mechanisms are unclear. We hypothesize that reversal of aging-induced downregulations of cardiac SR Ca 2+ -ATPase (SERCA2a) and β 1 -AR may lead to normalization of myocyte [Ca 2+ ] i regulation, β-AR regulation, and preserving normal myocyte function, thereby preventing aging-induced cardiac dysfunction and eliminating myocardial aging. Methods: We compared protein levels of β 1 - and β 3 -AR, and SERCA2a, myocyte contractile, [Ca 2+ ] i transient ([Ca 2+ ] iT ) and calcium current (I Ca,L ) responses to isoproterenol (ISO, 10 -8 M) in LV myocytes obtained from 2 young (Y) (~6 m) and 2 aged (A) (~28 m) groups (7/group) of wild-type (WT) and β 3 KO mice, respectively. Results: Compared with YWT, AWT myocytes had significantly decreased protein levels of SERCA2a (AWT: 0.24 vs YWT: 0.67), and β 1 -AR (0.35 vs 0.59), but increased β 3 -AR (0.36 vs 0.16) with reduced basal cell contraction (dL/dt max ) (85.3 vs 126.8μm/s), relaxation (dR/dt max ) (66.7 vs 102.1 μm/s), [Ca 2+ ] iT (0.18 vs 0.24), and I Ca,L (4.3 vs 7.6 pA/pF). These changes were accompanied by diminished ISO-stimulated inotropic response. In AWT myocytes, ISO caused significantly less increases in dL/dt max (34% vs 82%), dR/dt max (26% vs 64%), [Ca 2+ ] iT (16% vs 38%) and I Ca,L (15% vs 34%). Versus YWT, Yβ 3 KO did not alter basal myocyte contraction and relaxation and response to ISO stimulation, but had significantly increased protein levels of SERCA2a (1.41 vs 0.61) and unchanged β 1 -AR (0.65 vs 0.62). Aβ 3 KO mice had similar alterations. Importantly, in contrast to AWT, in Aβ 3 KO myocytes, there was increased SERCA2a (1.3) associated with normal basal cell contraction and relaxation, and preserved ISO-stimulated inotropic response. ISO caused similar increases in dL/dt max (Aβ 3 KO: 81% vs Yβ 3 KO: 83%), dR/dt max (68% vs 62%), [Ca 2+ ] iT (31% vs 32%) and I Ca,L (30% vs 32%). Conclusions: β 3 KO prevents aging-caused downregulations of cardiac β 1 -ARs and SERCA2a, leading to the preservation of myocyte function, [Ca 2+ ] iT , I Ca,L and β-adrenergic reserve in aged hearts. Thus, β 3 -AR may provide a new target for cardiac aging.
Abstract 9436: Treatment Options for Left Atrial Septal Pouch: A Case Report
Authors: Yaswanraj Yuvaraj, Michael Girard, VIANKA PEREZ
Journal: Circulation (2022)

Introduction: Left Atrial Septal pouch (LASP) is defined as an incomplete closure between the septum primum and septum secundum with an elongated septum secundum. This produces a crevice in the left atrium that functions as a source for static blood and atrial dissociation. This in turn could progress to the formation of thrombi within the left atrium that has the potential to embolize causing ischemic infarcts. Case Description: Here we present a 63 year old Hispanic female with a past medical history of paroxysmal atrial fibrillation on apixaban, recurrent strokes, dyslipidemia, and hypertension who presented with expressive aphasia, and prosopagnosia. Previously, the patient was reported of having two cardioembolic cerebral vascular accidents (CVA). Computed tomography of the brain demonstrated an old infarct of the left posterior parietal lobe. Patient was treated with intra-arterial tissue plasminogen activator of the left posterior cerebral artery and right middle cerebral artery. MRI demonstrated four acute punctate infarcts in the left frontal lobe consistent with embolic infarcts. TEE demonstrated a large patent foramen ovale (PFO), a prominent eustachian valve, and LASP. It was determined that her PFO and LASP were the culprit for her recurrent CVA despite appropriate AC. The PFO/LASP were successfully closed with an Amplatzer PFO occluder device. Patient was discharged home. Discussion: The LASP can function as a source of thrombus formation and atrial disassociation, which can cause embolic CVA. No guidelines exist on how to properly address a LASP. One option would be to use a PFO closure device to close LASP. Other options may include AC despite the absence of atrial fibrillation. Conclusions: In conclusion, further studies are necessary in order to establish the most appropriate management in patients with LASP.
Abstract 9453: The Role of Repeated PET/MRI Hybrid Imaging in Pulmonary Arterial Hypertension Patients Receiving Specific Therapy, Four-Year Observation
Authors: Remigiusz Kazimierczyk, Piotr Szumowski, Stephan Nekolla, Lukasz Malek, Piotr Blaszczak, Marcin hladunski, Bozena Sobkowicz, Janusz Mysliwiec, Karol Kaminski
Journal: Circulation (2022)

Introduction: PET/MRI hybrid imaging in pulmonary arterial hypertension (PAH) provides new prognostic parameters, which identify the group of patients who potentially might benefit from early PAH therapy escalation. In previous study we confirmed that right ventricle (RV) metabolic alterations are linked with PAH hemodynamics and both precede clinical deterioration. Hypothesis: Repeating PET/MRI scans improves PAH patients’ management. Methods: Twenty stable patients (49.9±14.9 y.o.) had second simultaneous PET/MRI scans during follow up visit (FU) after 24 months from baseline scans. SUV RV /SUV LV ratio was used to estimate and compare cardiac glucose uptake before and after PAH therapy escalation. Next, observation was extended to 48 months in total. Results: Between baseline and FU visits, 16 patients needed therapy escalation (mostly to prostacyclin); median SUV RV /SUV LV (observed in PET) has lowered with improvement in both RV ejection fraction (MRI) and mean pulmonary artery pressure (catheterization). In long observation (48 months) mean time to clinical worsening was 25.2±17.1 months. Cut-off value of PET-derived SUV RV /SUV LV in ROC analysis was 0.54, suggesting that even subtle shift in cardiac glucose metabolism in PAH may result in worse prognosis. PAH patients with baseline SUV RV /SUV LV higher than 0.54 had significantly worse prognosis in the 48-months observation (log-rank test, p=0.003). Finally, patients with follow-up SUV RV /SUV LV ratio higher than 1.14 had still significantly worse prognosis despite of previously escalated treatment during FU visits (log-rank test, p=0.04, Figure). Conclusions: Repeated PET/MRI imaging provides non-invasive assessment of PAH patients’ hemodynamics, prognosis and helps to determine effectiveness of targeted therapy affecting subtle cardiac metabolic changes. Even single PET/MRI assessment in PAH patients may help to determine long-term prognosis and to plan appropriate PAH therapy.
Abstract 9223: Self-Reported Efficacy in Patient-Physician Interaction in Relation to Anxiety, Patient Activation, and Self-Rated Health Among Smartwatch Users: The Pulsewatch Study
Authors: Jordy Mehawej, Khanh-van T Tran, Andreas Filippaios, Tenes Paul, Qiying Dai, Eric Ding, Sakeina Wilson, Syed Naeem, Jane Saczynski, Darleen Lessard, Essa Hariri, Edith Mensah Otabil, Kamran Noorishirazi, Carly Beniek, Apurv Soni, David D McManus
Journal: Circulation (2022)

Introduction: Early detection of AF is critical for stroke prevention. Several commercially available smartwatches are FDA cleared for AF detection; however, little is known about how use of a smartwatch impacts patient-physician relationships or patient anxiety, patient activation, and patient health-related quality of life. Hypothesis: Low self-reported efficacy in patient-physician interaction is associated with worse patient activation, increased anxiety, and lower self-rated quality of life. Methods: Data were used from the Pulsewatch study, a two-phased randomized controlled trial, which enrolled adults (&gt;50 years of age) with no contraindication to anticoagulation. The Perceived Efficacy in Patient-Physician Interactions (PEPPI) was used to assess patient confidence in physician interaction at baseline. Generalized Anxiety Disorder-7 Scale, Consumer Health Activation Index, and Short-Form Health Survey were utilized to examine anxiety, patient activation, and physical and mental health status, at baseline, 14, and 44 days, respectively. We used a mixed-effects repeated measures linear regression models to assess changes in anxiety, patient activation, and physical and mental health status in relation to self-reported efficacy in physician interaction, adjusting for confounding variables, over the study period. Results: A total of 93 participants (average age 64.1 ± 8.9 years; 43.0% female; 88.2% non-Hispanic white) were included in this analysis. 60% (n=56) of participants reported high perceived efficacy in patient-physician interaction. In the fully adjusted models, high perceived efficacy, vs low, was associated with an increased patient activation and mental health status (β 12.0, p-value &lt;0.001; β 3.39, p-value &lt;0.05, respectively), but was not associated with anxiety or physical health status (β -0.61, p-value 0.46; β 0.64, p-value 0.77). Conclusions: Our observation that higher self-efficacy leads to improved patient activation and mental health among stroke survivors suggest that self-efficacy is an important psychosocial marker. Efforts to improve perceived efficacy in patient-physician interaction in may lead to better clinical outcomes.
Abstract 9454: Cardiovascular Risks of Chemo-Immunotherapy for Lung Cancer: A Population-Based Cohort Study
Authors: Jeffrey S Chan, Hoi Kiu Pias Tang, Kenrick Ng, Edward Christopher Dee, Teddy Lee, Oscar Hou In Chou, Yan Hiu Athena Lee, Dawnie Ho Hei Lau, Tong Liu, Gary Tse
Journal: Circulation (2022)

Introduction: Chemo-immunotherapy combinations have proven efficacious for treating advanced lung cancer. However, their cardiovascular risks are unclear. This study thus aimed to compare the cardiovascular risks between programmed cell death protein 1 (PD-1) inhibitors, and chemo-immunotherapy in Asian patients with lung cancer. Methods: This retrospective cohort study included patients aged at least 18 years old with lung cancer receiving any PD-1 inhibitor in Hong Kong during 2013-2021. Patients with non-concurrent use of PD-1 inhibitor and chemotherapy, use of tyrosine kinase inhibitor, other immunotherapy, or those with prior stroke, heart failure, or myocardial infarction were excluded. Treatment groups were defined as PD-1 inhibitor only, and concurrent use of PD-1 inhibitor and chemotherapy (chemo-immunotherapy). The endpoint was major adverse cardiovascular events (MACE), that was the first occurrence of cardiovascular death, heart failure, stroke, or myocardial infarction. Patients were followed up until the end of 2021. Inverse probability treatment weighting (IPTW) was used to minimise covariate imbalances. Results: Of the 1508 patients identified, 713 were analysed (538 male, mean age 66.2±10.6 years old, mean follow up 1.4±1.3 years); 333 received PD-1 inhibitors only, and 380 received chemo-immunotherapy. IPTW achieved good balance for all covariates. The observed incidence rate of MACE was 2.8 events per 100 person-year (95% confidence interval (CI) 1.6-4.8) for patients on PD-1 inhibitors, and 2.1 per 100 person-year (95% CI 1.2-3.8) for those on chemo-immunotherapy. The log-rank test showed no significant difference in cumulative incidence of MACE between treatment groups (p=0.641; Figure 1). Conclusions: MACE may be uncommon amongst patients with lung cancer receiving PD-1 inhibitors or chemo-immunotherapy. The associated risks of MACE may not be significantly different between PD-1 inhibitors and chemo-immunotherapy.
Abstract 9231: Contribution of Echocardiographic Abnormalities to Cardiac Sarcoidosis Diagnosis According to Past and Contemporary Diagnostic Criteria
Authors: John Tremblay, Marc Judson, Mikhail Torosoff
Journal: Circulation (2022)

Introduction: Cardiac sarcoidosis (CS) guidelines were originally published in 1993 by the Japanese Ministry of Health and Welfare (JMHW) and updated in 2006 and 2017. The updated guidelines consider several echocardiographic abnormalities as major diagnostic CS criteria. Contribution of this change to CS diagnosis has not been well investigated. Methods: A case control, single tertiary medical center study included 571 sarcoidosis patients (52.7% females, 58.9+/-12.6 years old) with documented extracardiac sarcoidosis and completed electrocardiogram and imaging assessment. Echocardiographic abnormalities consistent with CS were left ventricular (LV) dilation (LVD), LV aneurysms (LVA), LV wall motion abnormalities (LVWMA), LV hypertrophy (LVH), right ventricular hypertrophy (RVH), focal thinning of the anterior septum, and LV ejection fraction (EF) less than 50%. Frequency of echocardiographic abnormalities according to 1993, 2006 and 2017 CS diagnostic criteria were compared. Results: Most common echocardiographic abnormalities were reduced LVEF and LVH, occurring in more than 14 and 12% of CS patients. LVD and LVWMA occurred 8 and 7%, followed by uncommon RVH, LVA, and septal thinning (Table). Despite being common in CS, only LVD, LWMA, and reduced LVEF significantly (p&lt;0.001) contributed to the CS diagnosis, while LVH did not (p=0.609). Alternatively, while LV aneurysm and septal thinning were uncommon, they significantly contributed to CS diagnosis (p&lt;0.001). RVH was very uncommon and did not affect CS diagnosis. Conclusions: CS diagnostic criteria highlights the importance of cardiac imaging in suspected CS. Commonly seen echocardiographic findings of CS include EF&lt;50%, LVWMA, and LV dilation significantly contribute to CS diagnosis. Of less commonly seen abnormalities, RVH utility appears to be low, while LVA and septal thinning may be helpful. Echocardiography remains an integral part in evaluating individuals with suspected CS.
Abstract 319: Computational Analysis Of Brain Imaging To Predict Post-arrest Brain Death
Authors: Nicholas P Case, Patrick J Coppler, Clifton W Callaway, Jonathan Elmer
Journal: Circulation (2022)

Background: Grey-white matter ratio ( GWR) can estimate severity of cerebral edema after cardiac arrest and predict progression to brain death. Current approaches to calculating GWR have variable interrater reliability. We tested if a computational technique to quantify the distribution of whole-brain x-ray attenuation at hospital admission could predict ultimate progression to brain death. Methods: We identified in- and out-of-hospital post-arrest patients at our single center treated between 2018-2019. We extracted demographic data from our registry and Digital Imaging and Communication in Medicine (DICOM) files for the first post-arrest CT. We analyzed the 17th slice of each DICOM, corresponding to the level of the basal ganglia. We extracted the 512x512 array of Hounsfield units (HU). We excluded HU &gt;40 or &lt;10 to focus on brain tissue densities. We summarized each patient’s distribution of HU and calculated the variance as a proxy for GWR. We randomly divided our data into 75% training set and 25% test set, used univariate logistic regression to predict brain death, identified a highly specific cutoff to rule out progression to brain death, and calculated test set sensitivity and specificity at this cutoff. We performed all analyses using Python. Results: Of 413 included patients, 163 (39%) were female, median [IQR] age was 63 [52 - 73] years, and 39 (9%) progressed to brain death. CTs were obtained a median [IQR] of 4.47 [3.03 to 6.35] hours post-arrest. HU variation predicted brain death with an area under the receiver operating characteristic curve (AUROC) of 0.81 in the training set and 0.88 in the test set. The odds ratio (OR) of progression to brain death with decreasing HU variation was 0.85 (95% confidence interval [CI], 0.80 - 0.91; P &lt; 0.001). A cutoff of 53.9 had a sensitivity of 36% (95% CI, 30.10% to 41.33%) at 97% specificity (95% CI, 89.91% to 100%) in the training set and a sensitivity of 45% (95% CI, 34.63% to 54.73%) at 100% specificity in the test set. Conclusion: Preserved HU variation excludes progression to brain death in comatose post-arrest patients with high specificity.
Abstract 9809: Clinical Outcomes of Transcatheter Aortic Valve Replacement vs.surgical Aortic Valve Replacement in Patients With Durable Left Ventricular Assist Device
Authors: Shazib Sagheer, Abdul Minhas, Syeda H Zaidi, Sourbha Dani, Sachin S Goel, mahboob alam, najam wasty
Journal: Circulation (2022)

Introduction: Patients with left ventricular assist device (LVAD) often develop aortic insufficiency (AI) requiring an intervention on the aortic valve. We sought to analyze the outcomes of patients with a history of LVAD who underwent either transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). Methods: The Nationwide Readmission Database (NRD) was used to extract relevant patient information from January 1, 2016, to December 31, 2018. The NRD is a nationally representative sample of all-payer discharges from U.S. non-federal hospitals. The primary outcome of interest was in-hospital mortality. Secondary outcomes included length of stay, inpatient outcomes, costs, and 30-day all-cause readmissions. Complex samples multivariable logistic and linear regression models were used to determine the association of procedure type with outcomes. Results: Among 148 hospitalizations with a history of LVAD, 87 underwent TAVR, and 61 underwent SAVR. The inpatient mortality in SAVR group was numerically higher compared to the TAVR cohort, however, it did not reach statistical significance. The use of invasive mechanical ventilation, cardiogenic shock, bleeding, and vascular complications were higher in the SAVR cohort compared to the TAVR cohort. The mean length of stay (in days) and costs were higher in the SAVR cohort compared to the TAVR cohort. The 30-day all-cause readmission rate was numerically higher in the SAVR group, however, it was not statistically significant (Table 1). Conclusions: TAVR in patients with LVAD is a viable treatment option for AI and potentially leads to better inpatient mortality and inpatient outcomes compared to patients who undergo SAVR.